Near infra-red selective photothermolysis for ectatic vessels and method therefor

ABSTRACT

Near-infrared selective photothermolysis for the treatment of ectatic blood vessels, for example, blood vessels of a portwine stain birthmark. This technique is especially applicable to deeper lying blood vessels in view of the better penetration of the near infrared light. Consequently, vessels are below a dermal/epidermal boundary can be reached. Near-infrared is defined as a range of approximately 700 to 1,200 nm. The optimal colors are near 760 or between 980 to 990 nm for most populations.

RELATED APPLICATION

[0001] This application is a Continuation of U.S. Ser. No. 08/720,267,filed Sep. 26, 1996, the entire teachings of which are incorporatedherein by reference, which is a Continuation of U.S. Ser. No.08/353,565, filed Dec. 9, 1994.

BACKGROUND OF THE INVENTION

[0002] Vascular lesions, comprising enlarged or ectatic blood vessels,pigmented lesions, and tattoos have been successfully treated withlasers for many years. In the process called selective photothermolysis,the targeted structure, the lesion tissue or tattoo pigment particles,and the surrounding tissue are collectively irradiated with laser light.The wavelength or color of this laser light, however, is chosen so thatits energy is preferentially absorbed into the target. Localized heatingof the target resulting from the preferential absorption leads to itsdestruction.

[0003] Most commonly in the context of vascular lesions, such asportwine stains for example, hemoglobin of red blood cells within theectatic blood vessels serves as the laser light absorber, i.e., thechromophore. These cells absorb the energy of the laser light andtransfer this energy to the surrounding vessels as heat. If this occursquickly and with enough energy, the surrounding vessels reach atemperature to denature their proteins. The fluence, Joules per squarecentimeter, to reach the denaturation of the vessels is calculated to bethat necessary to raise the temperature of the targeted volume withinthe vessel to about 70° C. before a significant portion of the absorbedlaser energy can diffuse out of the vessel. The fluence must, however,be limited so that the surrounding tissue is not also denatured.

[0004] As suggested, simply selecting the necessary fluence is notenough. The intensity and pulse duration of the laser light must also beoptimized for selectivity by both minimizing diffusion into thesurrounding tissue during the pulse while avoiding localizedvaporization. Boiling and vaporization are desirably avoided since theylead to mechanical, rather than chemical, damage—which can increaseinjury and hemorrhage in tissue surrounding the lesion. Theseconstraints suggest that the pulse duration should be longer with acorrespondingly lower intensity to avoid vaporization. Because ofthermal diffusivity, energy from the laser light pulse must be depositedquickly, however, to minimize heat dissipation into the surroundingtissue. The situation becomes more complex if the chromophore is theblood cell hemoglobin within the lesion blood vessels, since the vesselsare an order of magnitude larger than the blood cells. Radiation must beadded at low intensities so as to not vaporize the small cells, yet longenough to heat the blood vessels by thermal diffusion to the point ofdenaturation and then terminated before tissue surrounding the bloodvessels is damaged.

[0005] Conventionally, long pulse flashlamp excited dye lasers have beenused as the laser light source. These lasers have the high spectralbrightness required for selective photothermolysis and can be tuned tothe alpha absorption band of hemoglobin. Colors in the range of 577 to585 nm are absorbed well by the chromophore, the red blood cells in theblood vessels. Further, the relative absorption between the targetedblood and the melanin in the surrounding tissue is optimum in order tominimize heating of the melanin.

SUMMARY OF THE INVENTION

[0006] The implementation of dye lasers tuned to the conventional colorrange presents a number of drawbacks. Theory dictates that the length ofthe light pulse should be on the order of the thermal relaxation time ofthe ectatic vessels. Larger ectatic vessels, greater than 30 microns,consequently require pulse durations of 0.5 msec and longer.Commercially available dye lasers are limited in pulse durations toapproximately 0.5 msec and shorter, however. Further, current researchsuggests that pulse durations exceeding 0.7 msec are probably notattainable by these lasers. As a result, in selective photothermolysistreatment of these larger ectatic vessels, higher than optimum fluencesmust be used to compensate for the pulse duration limitations. Thisleads to temporary hyperpigmentation, viz., purpura. Moreover, the molarextinction coefficient, a measure of a chemical's optical absorptioncharacteristics, is approximately 0.2 for both melanin and hemoglobin inthe range of 577 to 585 nm. As a result, for fair Caucasian skin, forexample, the effective penetration depth of light in this wavelengthrange is limited to less than 0.5 mm. Therefore, the dye laser treatmenttechniques work exceptionally well on vascular lesions comprised ofvessels less than 30 microns in diameter and located above thedermal/epidermal junction. On the negative side, deep penetration islimited because of the high absorption, and multiple treatments arenecessary to get at deeper vessels. Further, as previously noted largevessels are sub-optimally treated with pulses that are too short intime.

[0007] The near infra-red portion of the electromagnetic spectrum,designated for the purposes of this description as stretching fromapproximately 700 to 1200 nm, provides regions of favorable ratiosbetween competing melanin and hemoglobin absorption. The use of thesewavelengths for the treatment of ectatic blood vessels has beenuniversally ignored as an alternative to the 577-585 nm wavelengthsbecause of the poor hemoglobin absorption characteristics in this area.This conclusion, however, fails to recognize that the ratio between theabsorption characteristics of the hemoglobin and the melanin is theprinciple variable in achieving selectivity, not net absorption.Moreover, in the treatment of deeper lying vessels, the poor absorptioncharacteristics can actually be an asset since it enables deeper overallpenetration of the laser light.

[0008] In light of the above, in general, according to one aspect, theinvention is directed to near-infrared selective photothermolysis forthe treatment of vascular lesions. In specific embodiments, thistechnique is used to treat ectatic blood vessels, for example, bloodvessels of a portwine stain birthmark. This technique is especiallyapplicable to deeper lying blood vessels in view of the betterpenetration of the near infrared light. Consequently, vessels below adermal/epidermal boundary can be reached.

[0009] In specific embodiments a few different wavelength ranges arepossible. Generally, the near-infrared light is in the range ofapproximately 700 to 1,200 nm. More specifically, the range can belimited to 750 to 780 nm. The best color is 760 nm, however.Alternatively, a general range of 980 to 990 nm is also effective.

[0010] The laser light is preferably generated by one of an alexandrite,titanium sapphire, chromium doped fluoride, or semiconductor diode laserand conveyed to the patient via an optical fiber delivery system fortransmitting the laser light to a patient.

[0011] In general according to another aspect, the invention features anear-infrared selective photothermolysis device for treatment of ectaticvascular lesions. This device comprises a laser system for generatingnear-infrared laser light pulse having a duration of greater than 0.2milliseconds and a delivery system for transmitting the laser lightpulse to a patient.

[0012] In specific embodiments, the laser system includes analexandrite, titanium sapphire, chromium doped fluoride, orsemi-conductor diode-type laser. If the pulse duration or power outputof the selected laser is inadequate individually, the light pulses frommultiple diode lasers, for example, can be combined. Time-multiplexingachieves long effective pulse durations. Consequently, effective pulsedurations of between 1 and 10 msec are achievable when individual laserdiodes only produce pulses of 0.5 msec. Combinations of simultaneouslygenerated beams increase effective power.

[0013] In general according to still another aspect, the inventionfeatures a method for treating a vascular lesion. This method comprisesirradiating the lesion with near-infrared laser light pulses. Theduration of these pulses is controlled to approximately match a thermalrelaxation time of blood vessels of the lesion. The near-infraredwavelengths stretch from approximately 700 to 1,200 nm.

[0014] The above and other features of the invention including variousnovel details of construction and combinations of parts, and otheradvantages, will now be more particularly described with reference tothe accompanying drawings and pointed out in the claims. It will beunderstood that the particular method and device embodying the inventionis shown by way of illustration and not as a limitation of theinvention. The principles and features of this invention may be employedin various and numerous embodiments without the departing from the scopeof the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] In the accompanying drawings, reference characters refer to thesame parts throughout the different views. The drawings are notnecessarily to scale; emphasis has instead been placed upon illustratingthe principles of the invention. Of the drawings:

[0016]FIG. 1 schematically shows a near-infrared selectivephotothermolysis device of the invention using a single laser;

[0017]FIG. 2 is a plot of the molar extinction coefficient as a functionof wavelength, in nanometers, for oxyhemoglobin HbO₂(solid line),deoxyhemoglobin Hb (dotted line), bilirubin (dashed line), andDOPA-melanin (the apparently exponentially falling solid line);

[0018]FIG. 3 schematically shows a near-infrared selectivephotothermolysis device of the invention using multiple laser diodes ordiode arrays; and

[0019]FIG. 4 is a plot of TiS laser output as a function of time fordifferent levels of flashlamp excitation, showing that relaxationoscillation is not a factor for long pulse durations.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] Turning now to the drawings, a near-infrared selectivephotothermolysis device 100, constructed according to the principles ofthe present invention, is illustrated in FIG. 1. This device 100 isgenerally similar to that found in the prior art except to the extentthat it includes a radiation source that generates light pulses in thenear-infrared region of the electromagnetic spectrum. More completely, alaser system 110 generates a beam of near-infrared light B, i.e., in therange of 700-1200 nm. The beam of light B is coupled into a deliverysystem 120, such as a single optical fiber, and transported to the skin50 of a patient. Because this light beam B is in the near-infraredregion of the spectrum, it can achieve substantial penetration beyond adermal/epidermal boundary 55 to treat an entire portion of a vascularlesion 60. This lesion 60 could be of one of many different types suchas portwine stain birthmarks, hemangiomas, telangiectasia, idiopathicvulvoddynia, and leg veins. Further, it could also be vessels in simplewrinkles, caused by age or sun exposure, or blood vessels in scartissue.

[0021] The pulse duration of the light beam B is matched to the thermalrelaxation time of the targeted ectatic vessels. Generally, thisrequires durations greater than 0.2 msec. For vessels of 30 microns indiameter and larger, as are present in portwine stains of adultpatients, the duration should ideally exceed 0.5 msec, whereas pulsedurations of 1 msec to 10 msec should be selected, if the vessels arelarger than 100 microns.

[0022] Referring to FIG. 2, there are a number of specific ranges withinthe near-infrared that will be especially effective in treating vascularlesions. (Because the molecular weights of melanin are poorly defined,the spectrum shown is the optical density on a scale of 0 to 1.5 for a1.5 mg % solution of DOPA-melanin.) FIG. 2 is a plot of the molarextinction coefficient as a function of wavelength in nanometers.

[0023] For an acceptable degree of selectivity in fair Caucasian skin,the ratio between the molar extinction coefficient of the hemoglobin andthe melanin should be at least 0.05. The ratio of combineddeoxyhemoglobin (Hb) and oxyhemoglobin (HbO₂) absorption to melaninabsorption (DOPA-melanin) is generally favorable, 0.05 or greater,between 700 and 1,200 nm. If the deoxyhemoglobin Hb is specificallytargeted, the wavelength range of 700 to 1,000 nm of the laser beam B isacceptable. The deoxyhemoglobin absorption peaks in the range of 750 to780 nm with the best ratios at approximately 760 nm.

[0024] The total absorption of hemoglobin is less in the near-infraredthan the conventional range of 577-585 nm. Therefore, fluences of thelight beam B required to treat ectatic vessels are higher than fluencesused with conventional shorter wavelengths. Therefore, the light beam Bgenerally provides fluences of between 2 and 20 J/cm².

[0025] The laser system 110 can comprise several candidate lasers, whichare available to generate the near-infrared laser light around 760 nm.For example, alexandrite is tunable within the range of 720-790 nm. Alsotunable titanium sapphire (TiS) produces light in the range of 720-950nm. These two lasers appear to be the best candidates since they arehighly developed under current technology. Other tunable chromium dopedfluoride lasers such as LiCaAlF₆, LiCaGaF₆, LiSrAlF₆, and LiSrGaF₆ inaddition to semiconductor diode lasers are also potential alternatives.

[0026] Alexandrite lasers are particularly well adapted to selectivephotothermolysis since pulse generation in the range of 3 to 10 msec ispossible. This pulse duration is most appropriate for the treatment ofectatic vessels of 100 microns and larger, which are ineffectivelytreated by currently available technology. These lasers, however,exhibit a very spiky behavior in the so-called normal mode of operation.This results from relaxation oscillation.

[0027] Semiconductor diode lasers do not store energy in a metastableupper laser level and consequently do not show the spiky behavior. Theindividual power output is, however, too low to reach the necessaryfluences which are necessary to treat ectatic vessels. Implementation ofdiode lasers requires the combination of beams from many lasers to reachthe more than 100 watts needed. Such an embodiment is schematicallyshown in FIG. 3 in which the outputs from three diode lasers 210, 212,214 of the laser system 205 are combined into a single beam and coupledinto the delivery system 220. The diode lasers 210-214, or TiS lasers,are coordinated by a synchronizer 230 that controls their respectivetimes of light generation. Alternatively, if still more power isrequired the diode lasers 210, 212, 214 are alternatively replaced withseparate arrays of diodes. In either case, the delivery system 220 is aliquid core flexible light guide instead of a single glass opticalfiber. These liquid core guides have large apertures, typically Smm andstill retain flexibility. Thus, beams from the several diode lasers, orseveral arrays, are directly focused onto the liquid light guide,greatly simplifying the transfer optics between the laser diodes and theectatic vessels.

[0028] Another device for combining many beams from diode lasers isspecifically disclosed in U.S. patent application Ser. No. 08/163,160,entitled, “Fault Tolerant Optical System Using Diode Laser Array,” ofwhich the present inventor is a co-inventor and which is incorporatedherein by this reference. This application is directed to the use ofcorrective micro-optics to mate a two-dimensional diode array with amasked-produced two-dimensional array of collimator micro-lens andmass-produced transformer sets.

[0029] The TiS laser is another viable candidate. In tests, these lasershave produced 1 to 5 msec pulses and did not exhibit the spiky behaviorthat is characteristic of flashlamp excited solid state laser systems.Most solid state lasers have an upper state lifetime of approximately100 μsec. In the TiS laser, however, this lifetime is only 3 μsec. As aresult, if the TiS lasing medium is pumped hard, as for example how dyelasers are pumped, the upper state becomes saturated and will not storeany more energy after about 2-3 μsec. This neutralizes most relaxationoscillation pulsing. For example, as shown in FIG. 4, four differentlevels of flashlamp excitation are demonstrated, 2,000, 1,800, 1,600,and 1400 V.D.C. The resulting pulse durations of two to three msec donot exhibit strong relaxation oscillation pulsing characteristics. Thepulses tended to be limited in duration to approximately 3 msec,however, by thermal lensing effects.

[0030] If individual TiS lasers are not capable of producing thenecessary pulse durations, the laser system 110 of FIG. 3 may timemultiplex the outputs of several lasers as taught in U.S. Pat. Ser. No.08/329,195, filed on Oct. 26, 1994, entitled “Ultra Long Pulsed DyeLaser for Treatment of Ectatic Vessels and Method Therefor,” of whichthe present inventor is a co-inventor and which is incorporated hereinby this reference. Specifically, the synchronizer 230 of FIG. 3sequentially triggers each of the diode or TiS lasers 210-214 to therebygenerate effective pulse durations. Alternatively or additionally, toachieve high effective power output, the synchronize 230 simultaneouslytriggers all of some of the lasers 210-214.

[0031] The deoxyhemoglobin HbO₂ can be specifically targeted, which hasa favorable absorption range between 800 and 1200 nm. The bestabsorption ratios exist between 980 and 990 nm. Here, the molarextinction coefficient of the oxyhemoglobin HbO₂ peaks and thecoefficient ratio of oxyhemoglobin to melanin actually exceeds 0.1. Thisis a desirable range for diode laser treatment. 50 watt fiber coupledcontinuous wave diode lasers, stand alone and fully developed, arecommercially available. These state of the art diode laser arrays canproduce 100 watts in a quasi-continuous wave mode. The pulse duration ofthese modes is typically around 400 μsec. Therefore, in the treatment oflarger ectatic vessels time-multiplexed arrays of diode lasers, asdescribed above, are necessary.

[0032] While this invention has been particularly shown and describewith references to preferred embodiments thereof, it will be understoodby those skilled in the art that various changes in form and details maybe made therein without departing from the spirit and scope of theinvention as defined by the appended claims.

I claim:
 1. A method for performing selective photothermolysis,comprising: generating near-infrared laser light; and treating vasculartargets with the laser light.
 2. A method as claimed in claim 1, furthercomprising treating ectatic blood vessels of vascular lesions with thelaser light.
 3. A method as claimed in claim 2, further comprisingtreating ectatic blood vessels of a portwine stain birthmark.
 4. Amethod as claimed in claim 1, further comprising generating the laserlight with a pulse duration of greater than 0.2 milliseconds.
 5. Amethod as claimed in claim 1, further comprising generating the laserlight with a pulse duration within a range of 1 to 10 milliseconds.
 6. Amethod as claimed in claim 1, comprising irradiating the targets withlaser light having a wavelength within a range of approximately 700 to1,200 nm.
 7. A method as claimed in claim 1, wherein the laser light hasa wavelength within a range of approximately 700 to 1000 nm.
 8. A methodas claimed in claim 1, wherein the laser light has a wavelength within arange of approximately 720-790 nm.
 9. A method as claimed in claim 1,wherein the laser light has a wavelength within a range of approximately750 to 780 nm.
 10. A method as claimed in claim 1, wherein the laserlight has a wavelength of approximately 760 nm.
 11. A method as claimedin claim 1, further comprising generating the laser light with analexandrite laser.
 12. A method as claimed in claim 1, furthercomprising generating the laser light with a titanium sapphire laser.13. A method as claimed in claim 1, further comprising generating thelaser light with a chromium-doped fluoride laser.
 14. A method asclaimed in claim 1, further comprising generating the laser light with asemiconductor diode laser.
 15. A method as claimed in claim 1, furthercomprising transmitting the laser light to the vascular target of apatient with an optical fiber delivery.
 16. A method as claimed in claim1, further comprising time multiplexing the output of at least one laserto generate the laser pulse.
 17. A near-infrared selectivephotothermolysis device for treatment of vascular lesions, the devicecomprising: a laser system for generating near-infrared laser lightpulses having durations greater than 0.2 milliseconds; and a deliverysystem for transmitting the laser light pulses to vascular targets of apatient.
 18. A device as claimed in claim 17, wherein the vasculartargets are ectatic blood vessels of a portwine stain birthmark.
 19. Adevice as claimed in claim 17, wherein the laser light pulses have awavelength in a range of approximately 700 to 1,200 nm.
 20. A device asclaimed in claim 17, wherein the laser light pulses have a wavelength ina range of approximately 700 to 1000 nm.
 21. A device as claimed inclaim 17, wherein the laser light pulses have a wavelength in a range ofapproximately 750 to 780 nm.
 22. A device as claimed in claim 17,wherein the laser light pulses have a wavelength of approximately 760nm.
 23. A device as claimed in claim 17, wherein the laser light pulseshave a wavelength in a range of approximately 800 to 1200 nm.
 24. Adevice as claimed in claim 17, wherein the laser light pulses have awavelength in a range of approximately 720-950 nm.
 25. A device asclaimed in claim 17, wherein the laser system comprises an Alexandritelaser.
 26. A device as claimed in claim 17, wherein the laser systemcomprises a titanium sapphire laser.
 27. A device as claimed in claim17, wherein the laser system comprises a chromium doped fluoride laser.28. A device as claimed in claim 17, wherein the laser system comprisesa semi-conductor diode laser.
 29. A device as claimed in claim 17,wherein the laser system multiplexes pulses from at least one laser togenerate a longer effective pulse duration.
 30. A device as claimed inclaim 17, wherein the delivery system comprises an optical fiber forcombining and delivering light from at least one laser.
 31. A device asclaimed in claim 17, wherein an effective pulse duration of the lightpulse is between 1 and 10 msec.
 32. A method for treating a vascularlesion, the method comprising: irradiating the lesion with near-infraredlaser light pulses; and controlling a duration of the pulses toapproximately match a thermal relaxation time of blood vessels of thetargets.
 33. A method as claimed in claim 32, further comprisinggenerating the laser light pulses at a wavelength in a range ofapproximately 720 to 790 nm.